(1R,2R,6R,8S)-8-(2-trimethylsilylethoxymethoxy)spiro[3,5,10-trioxatricyclo[6.2.1.02,6]undecane-4,1'-cyclohexane]-9-one | 185900-09-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (1R,2R,6R,8S)-8-(2-trimethylsilylethoxymethoxy)spiro[3,5,10-trioxatricyclo[6.2.1.02,6]undecane-4,1'-cyclohexane]-9-one
• CAS: 185900-09-8
• 化学式: C₁₉H₃₂O₆Si
• 分子量: 384.545
• InChiKey: BIFXNOOORNBRAE-XLMAVXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.22
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,2R,6R,8S)-8-(2-trimethylsilylethoxymethoxy)spiro[3,5,10-trioxatricyclo[6.2.1.02,6]undecane-4,1'-cyclohexane]-9-one 在 Rh/Al₂O₃ 盐酸 、 氢气 、 sodium hydride 、 二异丁基氢化铝 作用下， 以 1,4-二氧六环 、 正己烷 、 乙酸乙酯 、 甲苯 为溶剂， -30.0~25.0 ℃ 、101.33 kPa 条件下， 反应 52.0h， 生成 3-[(1S,3R,4R,5R)-1,3,4-trihydroxy-5-[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]oxycyclohexyl]propanoic acid
  参考文献：
  名称：

  Chlorogenic Acid and Synthetic Chlorogenic Acid Derivatives:  Novel Inhibitors of Hepatic Glucose-6-phosphate Translocase

  摘要：

  The enzyme system glucose-6-phosphatase (EC 3.1.3.9) plays a major role in the homeostatic regulation of blood glucose. It is responsible for the formation of endogenous glucose originating from gluconeogenesis and glycogenolysis. Recently, chlorogenic acid was identified as a specific inhibitor of the glucose-6-phosphate translocase component (G1-6-P translocase) of this enzyme system in microsomes of rat liver. Glucose B-phosphate hydrolysis was determined in the presence of chlorogenic acid or of new synthesized derivatives in intact rat liver microsomes in order to assess the inhibitory potency of the compounds on the translocase component. Variation in the 3-position of chlorogenic acid had only poor effects on inhibitory potency. Introduction of lipohilic side chain in the 1-position led to 100-fold more potent inhibitors. Functional assays on isolated perfused rat liver with compound 29i, a representative of the more potent derivatives, showed a dose-dependent inhibition of gluconeogenesis and glycogenolyosis, suggesting glucose-6-phosphatase as the locus of interference of the compound for inhibition of hepatic glucose production also in the isolated organ model. G1-6-P translocase inhibitors may be useful for the reduction of inappropriately high rates of hepatic glucose output often found in non-insulin-dependent diabetes.

  DOI：

  10.1021/jm9607360
• 作为产物：
  描述：

  右旋奎宁酸 在 硫酸 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 (1R,2R,6R,8S)-8-(2-trimethylsilylethoxymethoxy)spiro[3,5,10-trioxatricyclo[6.2.1.02,6]undecane-4,1'-cyclohexane]-9-one
  参考文献：
  名称：

  Chlorogenic Acid and Synthetic Chlorogenic Acid Derivatives:  Novel Inhibitors of Hepatic Glucose-6-phosphate Translocase

  摘要：

  The enzyme system glucose-6-phosphatase (EC 3.1.3.9) plays a major role in the homeostatic regulation of blood glucose. It is responsible for the formation of endogenous glucose originating from gluconeogenesis and glycogenolysis. Recently, chlorogenic acid was identified as a specific inhibitor of the glucose-6-phosphate translocase component (G1-6-P translocase) of this enzyme system in microsomes of rat liver. Glucose B-phosphate hydrolysis was determined in the presence of chlorogenic acid or of new synthesized derivatives in intact rat liver microsomes in order to assess the inhibitory potency of the compounds on the translocase component. Variation in the 3-position of chlorogenic acid had only poor effects on inhibitory potency. Introduction of lipohilic side chain in the 1-position led to 100-fold more potent inhibitors. Functional assays on isolated perfused rat liver with compound 29i, a representative of the more potent derivatives, showed a dose-dependent inhibition of gluconeogenesis and glycogenolyosis, suggesting glucose-6-phosphatase as the locus of interference of the compound for inhibition of hepatic glucose production also in the isolated organ model. G1-6-P translocase inhibitors may be useful for the reduction of inappropriately high rates of hepatic glucose output often found in non-insulin-dependent diabetes.

  DOI：

  10.1021/jm9607360

文献信息

• Chlorogenic Acid and Synthetic Chlorogenic Acid Derivatives:  Novel Inhibitors of Hepatic Glucose-6-phosphate Translocase
  作者：Horst Hemmerle、Hans-Joerg Burger、Peter Below、Gerrit Schubert、Robert Rippel、Peter W. Schindler、Erich Paulus、Andreas W. Herling

  DOI：10.1021/jm9607360

  日期：1997.1.1

  The enzyme system glucose-6-phosphatase (EC 3.1.3.9) plays a major role in the homeostatic regulation of blood glucose. It is responsible for the formation of endogenous glucose originating from gluconeogenesis and glycogenolysis. Recently, chlorogenic acid was identified as a specific inhibitor of the glucose-6-phosphate translocase component (G1-6-P translocase) of this enzyme system in microsomes of rat liver. Glucose B-phosphate hydrolysis was determined in the presence of chlorogenic acid or of new synthesized derivatives in intact rat liver microsomes in order to assess the inhibitory potency of the compounds on the translocase component. Variation in the 3-position of chlorogenic acid had only poor effects on inhibitory potency. Introduction of lipohilic side chain in the 1-position led to 100-fold more potent inhibitors. Functional assays on isolated perfused rat liver with compound 29i, a representative of the more potent derivatives, showed a dose-dependent inhibition of gluconeogenesis and glycogenolyosis, suggesting glucose-6-phosphatase as the locus of interference of the compound for inhibition of hepatic glucose production also in the isolated organ model. G1-6-P translocase inhibitors may be useful for the reduction of inappropriately high rates of hepatic glucose output often found in non-insulin-dependent diabetes.